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dc.contributor.authorViny, Aaron D.
dc.contributor.authorLiu, Yu
dc.contributor.authorDekker, Job
dc.contributor.authorLevine, Ross L.
dc.date2022-08-11T08:10:59.000
dc.date.accessioned2022-08-23T17:27:32Z
dc.date.available2022-08-23T17:27:32Z
dc.date.issued2019-08-30
dc.date.submitted2019-10-07
dc.identifier.citation<p>Cell Stem Cell. 2019 Aug 30. pii: S1934-5909(19)30338-8. doi: 10.1016/j.stem.2019.08.003. [Epub ahead of print] <a href="https://doi.org/10.1016/j.stem.2019.08.003">Link to article on publisher's site</a></p>
dc.identifier.issn1875-9777 (Linking)
dc.identifier.doi10.1016/j.stem.2019.08.003
dc.identifier.pmid31495782
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49886
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractTranscriptional regulators, including the cohesin complex member STAG2, are recurrently mutated in cancer. The role of STAG2 in gene regulation, hematopoiesis, and tumor suppression remains unresolved. We show that Stag2 deletion in hematopoietic stem and progenitor cells (HSPCs) results in altered hematopoietic function, increased self-renewal, and impaired differentiation. Chromatin immunoprecipitation (ChIP) sequencing revealed that, although Stag2 and Stag1 bind a shared set of genomic loci, a component of Stag2 binding sites is unoccupied by Stag1, even in Stag2-deficient HSPCs. Although concurrent loss of Stag2 and Stag1 abrogated hematopoiesis, Stag2 loss alone decreased chromatin accessibility and transcription of lineage-specification genes, including Ebf1 and Pax5, leading to increased self-renewal and reduced HSPC commitment to the B cell lineage. Our data illustrate a role for Stag2 in transformation and transcriptional dysregulation distinct from its shared role with Stag1 in chromosomal segregation.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=31495782&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1016/j.stem.2019.08.003
dc.subjectCohesin
dc.subjectStag1
dc.subjectStag2
dc.subjectchromatin
dc.subjecthematopoietic stem cells
dc.subjectmouse models
dc.subjectmyelodysplasia
dc.subjectnuclear topology
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectCancer Biology
dc.subjectCell Biology
dc.subjectGenetic Phenomena
dc.subjectGenetics and Genomics
dc.subjectMolecular Biology
dc.subjectStructural Biology
dc.subjectSystems Biology
dc.titleCohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation
dc.typeJournal Article
dc.source.journaltitleCell stem cell
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/sysbio_pubs/157
dc.identifier.contextkey15506533
html.description.abstract<p>Transcriptional regulators, including the cohesin complex member STAG2, are recurrently mutated in cancer. The role of STAG2 in gene regulation, hematopoiesis, and tumor suppression remains unresolved. We show that Stag2 deletion in hematopoietic stem and progenitor cells (HSPCs) results in altered hematopoietic function, increased self-renewal, and impaired differentiation. Chromatin immunoprecipitation (ChIP) sequencing revealed that, although Stag2 and Stag1 bind a shared set of genomic loci, a component of Stag2 binding sites is unoccupied by Stag1, even in Stag2-deficient HSPCs. Although concurrent loss of Stag2 and Stag1 abrogated hematopoiesis, Stag2 loss alone decreased chromatin accessibility and transcription of lineage-specification genes, including Ebf1 and Pax5, leading to increased self-renewal and reduced HSPC commitment to the B cell lineage. Our data illustrate a role for Stag2 in transformation and transcriptional dysregulation distinct from its shared role with Stag1 in chromosomal segregation.</p>
dc.identifier.submissionpathsysbio_pubs/157
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentProgram in Systems Biology


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